2oa0
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Crystal structure of Calcium ATPase with bound ADP and cyclopiazonic acid
OverviewOverview
The sarcoplasmic reticulum Ca(2+)-ATPase is essential for calcium reuptake, in the muscle contraction-relaxation cycle. Here we present structures of, a calcium-free state with bound cyclopiazonic acid (CPA) and magnesium, fluoride at 2.65 A resolution and a calcium-free state with bound CPA and, ADP at 3.4A resolution. In both structures, CPA occupies the calcium, access channel delimited by transmembrane segments M1-M4. Inhibition of, Ca(2+)-ATPase is stabilized by a polar pocket that surrounds the tetramic, acid of CPA and a hydrophobic platform that cradles the inhibitor. The, calcium pump residues involved include Gln(56), Leu(61), Val(62), and, Asn(101). We conclude that CPA inhibits the calcium pump by blocking the, calcium access channel and immobilizing a subset of transmembrane helices., In the E2(CPA) structure, ADP is bound in a distinct orientation within, the nucleotide binding pocket. The adenine ring is sandwiched between, Arg(489) of the nucleotide-binding domain and Arg(678) of the, phosphorylation domain. This mode of binding conforms to an adenine, recognition motif commonly found in ATP-dependent proteins.
About this StructureAbout this Structure
2OA0 is a Single protein structure of sequence from Oryctolagus cuniculus with MG, CZA and ADP as ligands. Active as Calcium-transporting ATPase, with EC number 3.6.3.8 Full crystallographic information is available from OCA.
ReferenceReference
The molecular basis for cyclopiazonic acid inhibition of the sarcoplasmic reticulum calcium pump., Moncoq K, Trieber CA, Young HS, J Biol Chem. 2007 Mar 30;282(13):9748-57. Epub 2007 Jan 26. PMID:17259168
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